Variation In Prostate-specific Antigen Levels Research Articles

Presence of PSA auto-antibodies in men with prostate abnormalities (prostate cancer/benign prostatic hyperplasia/prostatitis)

Prostate-specific antigen (PSA), produced by the prostate, liquefies post-ejaculate semen. PSA is detected in semen and blood. Increased circulating PSA levels indicate prostate abnormality [prostate cancer (PC), benign prostatic hyperplasia (BPH), prostatitis (PTIS)], with variance among individuals. As the prostate has been proposed as an immune organ, we hypothesise that variation in PSA levels among men may be due to presence of auto-antibodies against PSA. Sera from healthy men (n=28) and men having prostatitis (n=25), BPH (n=30) or PC (n=29) were tested for PSA antibody presence using enzyme-linked immunosorbent assay (ELISA) values converted to standard deviation (SD) units, and Western blotting. Taking ≥2 SD units as cut-off for positive immunoreactivity, 0% of normal men, 0% with prostatitis, 33% with BPH and 3.45% with PC demonstrated PSA antibodies. One-way analysis of variance (anova) performed on the mean absorbance values and SD units of each group showed BPH as significantly different (P<0.01) compared with PC and prostatitis. All others were nonsignificant (P<0.05). Men (33%) with BPH had PSA antibodies by ELISA and Western blot. These discoveries may find clinical application in differential diagnosis among prostate abnormalities, especially differentiating BPH from prostate cancer and prostatitis.

Changes in Serum PSA During Normal Menstrual Cycle

Prostate specific antigen (PSA) has long been used as a biological marker for prostatic cancer. Recent studies have demonstrated that PSA synthesis can be induced by steroid hormones in several tissues of women. Menstrual cycle is regulated by the cyclic variation of estradiol and progesterone. This study was undertaken in order to study the correlation of serum PSA to both these corpus luteal hormones. 110 serum samples and 10 saliva samples were collected from healthy women aged 18-45years of age having normal menstrual cycles. Active PSA DSL-9700 ultrasensitive kit with detection limit 0.001ng/ml was used to analyze PSA. 38.2% of all serum samples and 10% of saliva samples had detectable concentrations of PSA. The serum PSA was highest during mid follicular phase (between 4th and 8th days of cycle). Variation in PSA levels seemed to follow the variations in progesterone with a lag period of 12-14days, but did not appear to bear any relationship with the estradiol levels.

Seasonal variation in prostate-specific antigen levels: a large cross-sectional study of men in the UK

• To assess whether a seasonal change in prostate specific antigen (PSA) levels can be detected in men recruited to a large clinical trial. • A total of 66 969 men aged 50-69 years were drawn from a large study conducted at general practices across the UK between 2002 and 2007. • Trigonometric algorithms and regression methods were used to assess the relationship between the time of year and serum PSA and blood pressure measurements. • We obtained local daily mean temperatures and hours of sunlight per day to assess whether these factors were potential mechanisms for seasonal variation in PSA levels or blood pressure. • The proportion of participants who would be considered clinically at risk according to their PSA or blood pressure measurement, by month, was also assessed. • The strength of associations between time of year and blood pressure were used to reinforce conclusions from the PSA models. • There was no relationship between time of year and PSA levels (P= 0.11) or between climate and PSA levels (P= 0.42). • No difference was found in the prevalence of clinically raised PSA content by month (P= 0.50). • This lack of an association with PSA content was despite our data being sufficient to provide clear evidence of an association between blood pressure and time of year (systolic P < 0.001; diastolic P < 0.001), and to show that this association was largely explained by climatic factors (temperature and sunlight). • There was no pattern in PSA levels by time of year, air temperature or levels of sunlight in this cohort, so there is no need to take these factors into account when reviewing PSA results.

Prostate-specific antigen kallikrein and the heart

Currently, there is growing interest regarding prostate-specific antigen (PSA) and the cardiovascular system. Increased PSA serum levels have been reported after prolonged cardiopulmonary resuscitation, cardiac surgery, extracorporeal cardiopulmonary bypass, acute myocardial infarction (AMI) and coronary artery stenting. The possible role of PSA in cardiac events has been questioned due to the finding of PSA decrease during AMI and by the correlation of variation in PSA levels with coronary lesions and occurrence of major adverse cardiac events. Complexed PSA forms and uncomplexed PSA forms are observed in the bloodstream but the increasing formation of irreversible bound PSA seems to be a crucial finding during AMI. Large studies need to be carried out to confirm these preliminary results and to elucidate unclear aspects. These findings present many potential directions for future research including the role of uncomplexed forms of PSA, the possible distribution of PSA in the heart, the relative expression levels in heart disease states, the mode of expression regulation and other potential specific substrates. The journey of PSA investigation could be longer than initially expected.

Clinical implications of introducing a new PSA assay

A number of different prostate-specific antigen (PSA) assays are in common use. There has been little consideration of the possible clinical implications of interassay variation. The availability of two assays in the same laboratory provided an opportunity to audit the clinical implications of the interassay variation in PSA levels. The same serum samples from patients with prostate cancer on follow-up were analyzed for PSA by the Abbott AxSYM assay and by the Abbott ARCHITECT assays. To assess within-patient reproducibility of the interassay variation, repeat analysis of PSA by both assays was conducted in a second sample obtained at least 1 month after the first. Samples from 156 cases were analyzed. The mean ratio of serum PSA values by the two assays (AxSYM assay/ARCHITECT assay) was 0.89 (range 0.5-2.27). The interassay coefficient of variation was 20%. In a subgroup of 50 cases with repeat samples available, the correlation coefficient, r, of the interassay variation in PSA between the first and second samples was 0.441. Interassay variation in serum PSA is clinically significant, both between patients and on repeated measurement within the same patient. Clinicians should be aware that simple correction factors may not accurately control for variation between PSA assays. Ideally, patients on follow-up for prostate cancer should be monitored using a single PSA assay.

Assessment of intra‐individual variation in prostate‐specific antigen levels in a biennial randomized prostate cancer screening program in Sweden

The degree of variability in prostate-specific antigen (PSA) measurements is important for interpreting test results in screening programs, and particularly for interpreting the significance of changes between repeated tests. This study aimed to determine the long-term intra-individual variation for PSA in healthy men. A randomly selected cohort of men in a biennial prostate cancer screening program (ERSPC) conducted in Sweden from 1995-1996 to 2001-2002. We studied men who had total PSA (tPSA) levels < 2.0 ng/ml in 2001-2002. This included 791 men with tPSA < or = 0.61 ng/ml (group A), 1,542 men with tPSA < or = 0.99 ng/ml (group B), and 1,029 men with tPSA 1.00-1.99 ng/ml (group C). The intra-individual variability of free PSA (fPSA) and tPSA was assessed by calculating coefficients of variation (CV) for each individual's PSA measurements from the first and second round of screening (1995-1996 and 1997-1998). Intra-individual CV (geometric means) for tPSA were 13.7%, 12.7%, and 11.5% in groups A, B, and C, respectively. Corresponding CVs for fPSA were significantly lower, ranging from 12.1% to 10.4%. The estimated biological variation of tPSA and fPSA in groups A to C were 12.5%, 11.4%, 10.0% and 9.7%, 7.8%, 7.5%, respectively. In healthy men with PSA levels less than 2 ng/ml, the natural long-term variability for tPSA was less than 14%, and with 95% probability, a change in tPSA greater than 30% indicates a change beyond normal random variation.

Association between genetic polymorphisms in the prostate-specific antigen gene promoter and serum prostate-specific antigen levels.

Recent evidence suggests that genetic variation in the promoter of the prostate-specific antigen (PSA) gene may contribute to individual variation in serum PSA levels. However, polymorphisms associated with variations in PSA levels have not been identified. We used the polymerase chain reaction to amplify the promoter region of the PSA genes (nucleotide positions -3873 to -5749 with respect to the start of transcription) of 409 healthy white men at risk for lung disease. Polymerase chain reaction products were sequenced to identify polymorphisms in the PSA gene promoter and to genotype the men for common single nucleotide polymorphisms (SNPs) and were cloned into luciferase reporter constructs to assay PSA promoter activity in human LNCaP prostate cancer cells. Analysis of variance was used to test the association of polymorphism frequencies with mean serum PSA levels. All statistical tests were two-sided. The -4643G/A SNP (G allele) had a 21.2% prevalence and was associated with increases in serum PSA levels (P =.017) and PSA promoter activity (P<.001). The -5412C/T SNP (C allele) had a 22.0% prevalence and was associated with an increase in serum PSA levels (P =.0015). The -5429T/G SNP (G allele) had a 23.0% prevalence, was associated with an increase in serum PSA levels (P =.021), and was in linkage disequilibrium with the -5412C/T SNP. The promoter activity of the -5412 C/-5429 G haplotype was higher than that of the -5412 T/-5429 T haplotype (P<.001). Genetic variations in the PSA promoter are associated with serum PSA levels in men without prostatic disease. PSA promoter genotype information may help to refine models of PSA cutoff values.